Tiny magnetic particles from air pollution have for the first time been discovered to be lodged in human brains– and researchers think they could be a possible cause of Alzheimer’s disease.
Researchers at Lancaster University found abundant magnetite nanoparticles in the brain tissue from 37 individuals aged three to 92-years-old who lived in Mexico City and Manchester. This strongly magnetic mineral is toxic and has been implicated in the production of reactive oxygen species (free radicals) in the human brain, which are associated with neurodegenerative diseases including Alzheimer’s disease.
Professor Barbara Maher, from Lancaster Environment Centre, and colleagues (from Oxford, Glasgow, Manchester and Mexico City) used spectroscopic analysis to identify the particles as magnetite. Unlike angular magnetite particles that are believed to form naturally within the brain, most of the observed particles were spherical, with diameters up to 150 nm, some with fused surfaces, all characteristic of high-temperature formation – such as from vehicle (particularly diesel) engines or open fires.
The spherical particles are often accompanied by nanoparticles containing other metals, such as platinum, nickel, and cobalt.
Professor Maher said: “The particles we found are strikingly similar to the magnetite nanospheres that are abundant in the airborne pollution found in urban settings, especially next to busy roads, and which are formed by combustion or frictional heating from vehicle engines or brakes.”
Other sources of magnetite nanoparticles include open fires and poorly sealed stoves within homes. Particles smaller than 200 nm are small enough to enter the brain directly through the olfactory nerve after breathing air pollution through the nose.
“Our results indicate that magnetite nanoparticles in the atmosphere can enter the human brain, where they might pose a risk to human health, including conditions such as Alzheimer’s disease,” added Professor Maher.
Leading Alzheimer’s researcher Professor David Allsop, of Lancaster University’s Faculty of Health and Medicine, said: “This finding opens up a whole new avenue for research into a possible environmental risk factor for a range of different brain diseases.”
A team of researchers has built a mathematical model that describes the molecular events associated with the beginning stage of learning and memory formation in the human brain.
The research, published in the journal Proceedings of the National Academy of Sciences, paves the way for understanding cognitive function and neurodegenerative diseases—at the molecular and cellular levels.
The study focuses on the dynamics of dendritic spines, which are thorny structures that allow neurons to communicate with each other. When a spine receives a signal from another neuron, it responds by rapidly expanding in volume—an event called transient spine expansion.
Transient spine expansion is one of the early events leading up to learning and memory formation. It consists of a cascade of molecular processes spanning four to five minutes, beginning when a neuron sends a signal to another neuron.
Many of the molecular processes leading up to transient spine expansion have already been identified experimentally and reported in the literature. Here, the authors built a map of many of these known processes into a computational framework.
“Spines are dynamic structures, changing in size, shape and number during development and aging. Spine dynamics have been implicated in memory, learning and various neurodegenerative and neurodevelopmental disorders, including Alzheimer’s, Parkinson’s and autism. Understanding how the different molecules can affect spine dynamics can eventually help us demystify some of these processes in the brain,” said Padmini Rangamani, a mechanical engineering professor at the University of California San Diego and first author of the study.
“This work shows that dendritic spines, which are sub-micrometer compartments within individual neurons, are the prime candidates for the initial tag of transient, millisecond synaptic activity that eventually orchestrates memory traces in the brain lasting tens of years,” said Shahid Khan, senior scientist at the Molecular Biology Consortium at Lawrence Berkeley National Laboratory and a co-author on the PNAS paper.
In this study, researchers constructed a mathematical model, based on ordinary differential equations, linking the different molecular processes associated with spine expansion together. They identified the key components (molecules and enzymes) and chemical reactions that regulate spine expansion.
As a result, they observed an interesting pattern—that the same components could both turn on and off some of the steps in the sequence—a phenomenon called paradoxical signaling. Further, they linked the chemical reactions of the different molecules to the reorganization of the actin cytoskeleton, which gives the cell its shape.
Both of these features—paradoxical signaling and linking spine expansion to actin reorganization—make this model robust, Rangamani explained. “By putting all these complicated pieces together in a simple mathematical framework, we can start to understand the underlying mechanisms of spine expansion. This is one of the benefits of combining mechanics of the cytoskeleton and biochemistry. We can bring together pieces of experimental work that are often not seen. However, we should note that we are only at the beginning stages of understanding what spines, neurons and the brain can do.”
“This work is notable for bringing together aspects from diverse disciplines (systems biology, cell signaling, actin mechanobiology and proteomics) and should motivate similar multi-disciplinary efforts for other problems in fundamental cellular neuroscience,” Khan said.